Most thyroid nodules are benign. The ideal follow-up of these patients should reflect their prognosis, which has been scarcely investigated. We aimed to evaluate the prognosis of patients with initial benign thyroid cytology. A population-based study, using the Rochester Epidemiology Project, identifying patients with benign thyroid cytology diagnosed between 2003 and 2006 and completely followed to 2014 using linked medical records. We identified 363 thyroid nodules with benign cytology in 327 patients after fine-needle aspiration biopsy. Patients were on average 53 years old (standard deviation 17), and 80 % were women. The median nodule size was 1.6 cm (interquartile range 1.2–2.4); 26 % had at least one suspicious ultrasound feature. During a median follow-up of 8 years, 54 patients (17 %) with 57 benign nodules underwent thyroidectomy, mostly due to compressive symptoms (44 %). Thyroidectomy was more likely in younger patients [hazard ratio (HR) 0.97, 95 % CI 0.96–0.99] and patients with larger nodules (HR 1.3, 95 % CI 1.16–1.48). Two patients were found to have follicular thyroid cancer in the index nodule (0.6 %) and 6 patients had papillary thyroid cancer detected in other nodules (1.8 %). No patient died from thyroid cancer. Patients with benign thyroid nodules are unlikely to suffer morbidity or mortality due to thyroid cancer. Follow-up strategies for these patients should consider this excellent prognosis and avoid causing unnecessary fear in patients and adding unneeded expense and burden to the healthcare system.